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Randomized Controlled Trial
. 2025 May;27(5):872-880.
doi: 10.1002/ejhf.3348. Epub 2024 Jun 19.

Characterization of serum phosphate levels over time with intravenous ferric carboxymaltose versus placebo as treatment for heart failure with reduced ejection fraction and iron deficiency: An exploratory prospective substudy from HEART-FID

Nina Nouhravesh  1   2 , Jyotsna Garg  1 , Frank W Rockhold  1 , Carmine G De Pasquale  3 , Eileen O'Meara  4 , Gregory D Lewis  5 , Javed Butler  6 , Josephine Harrington  1 , Justin A Ezekowitz  7 , Piotr Ponikowski  8 , Richard W Troughton  9 , Yee Weng Wong  10 , Nicole Blackman  11 , Syed Numan  11 , Robert Adamczyk  11 , Adrian F Hernandez  1 , Robert J Mentz  1
Affiliations
Randomized Controlled Trial

Characterization of serum phosphate levels over time with intravenous ferric carboxymaltose versus placebo as treatment for heart failure with reduced ejection fraction and iron deficiency: An exploratory prospective substudy from HEART-FID

Nina Nouhravesh et al. Eur J Heart Fail. 2025 May.

Abstract

Aims: Ferric carboxymaltose (FCM) is guideline-recommended for iron deficiency (ID) in heart failure with reduced ejection fraction (HFrEF). Despite a well-established safety profile, the magnitude and clinical significance of FCM-induced hypophosphataemia in HFrEF remains unclear. This pre-specified substudy of HEART-FID evaluated serum phosphate, 1,25-dihydroxyvitamin D, and plasma parathyroid hormone (PTH) subsequent to FCM.

Methods and results: HEART-FID was a randomized, double-blind, placebo-controlled trial of ambulatory patients with HFrEF and ID randomized to FCM versus placebo. This substudy assessed mean change from baseline across eight visits over 6 months for the following endpoints: serum phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and PTH, in addition to the clinical severity of potential hypophosphataemia. Overall, 133 patients (n = 62 FCM, n = 71 placebo) were prospectively enrolled. Mean age was 68 ± 11 years, 55 (41.4%) were women, and 29 (21.8%) had chronic kidney disease. Phosphate levels decreased in 34 (57.6%) patients in the FCM group compared with 7 (10.3%) in the placebo group. Mean change in phosphate levels reached a nadir at day 21 (-0.36 ± 0.27 mmol/L) subsequent to FCM infusion with 28 (51%) having moderate-to-severe hypophosphataemia. Reductions in 1,25-dihydroxyvitamin D were also observed, whilst PTH increased. These biochemical changes returned to baseline levels by day 91. Serum levels of 25-hydroxyvitamin D remained stable throughout the study. No serious adverse events associated with hypophosphataemia were reported.

Conclusions: Transient moderate-to-severe hypophosphataemia was frequent subsequent to FCM infusion, accompanied by 1,25-dihydroxyvitamin D decrease and PTH increase. Serum levels of 25-hydroxyvitamin D remained stable. No evidence of symptomatic hypophosphataemia was reported, collectively indicating FCM-related hypophosphataemia to be clinically benign and transient in HFrEF.

Keywords: Ferric carboxymaltose; Heart failure with reduced ejection fraction; Hypophosphataemia.

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Figures

Figure 1
Figure 1
Flowchart of the study cohort. FCM, ferric carboxymaltose.
See this image and copyright information in PMC

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References

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